Oxalate is a difficult molecule to metabolize. Humans, for example, are unable to breakdown oxalate, an inability that is associated with kidney stones and crystalline arthritis. In this talk, we consider a recently discovered pathway for anaerobic microbial oxalate mechanism in which oxalate is cleaved to generate two molecules of carbon dioxide and two low-potential electrons by the thiamine pyrophosphate (TPP)-dependent enzyme oxalate oxidoreductase (OOR). Both the carbon dioxide and electrons produced by OOR feed into the microbial Wood-Ljungdahl pathway of acetogenesis. To understand the molecular basis for oxalate oxidation by OOR, we have obtained a series of crystallographic snapshots along the reaction coordinate. These structures, in addition to a structure of substrate-free OOR, have allowed us to visualize how active-site rearrangements can drive catalysis. Based on these crystallographic data, we propose that OOR operates via a bait-and-switch mechanism, attracting substrate into the active site through the presence of positively charged and polar residues, and then altering the electrostatic environment through loop and side chain movements to drive catalysis. This simple but elegant mechanism explains how oxalate, a molecule that humans and most animals cannot breakdown, can be used for growth by acetogenic bacteria.

Bait-and-switch mechanism in microbial oxalate metabolism

254th National Meeting (2017)

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